A model is proposed to explain the mechanism by which amphetamine releases biogenic amines from nerve endings of brain tissue. In this model, the neuronal uptake of amphetamine as well as biogenic amines is carrier mediated. Upon entering the neuron, amphetamine displaces biogenic amines from storage vesicles. The displaced amine binds to the carrier, which is now on the inside of the membrane, and the amine is transported out of the nerve ending. This model will be examined both in untreated synaptosomes and in synaptosomes in which the transport properties have been altered. Preliminary experiments have demonstrated that the buoyant density of synaptosomes can be altered by prior incubation with biogenic amines. This could provide a mechanism by which a specific subpopulation of synaptosomes can be differentiated from other synaptosomes. Experiments are proposed to examine whether this effect is due to a change in the osmotic properties of the synaptosomes. Preliminary experiments are also presented in which the transport properties of nerve endings have been altered in neonatal rats which have been exposed to a diet containing large amounts of saturated fats. This procedure results in a large decrease in the affinity of the transport system for norepinephrine. Experiments are described in which this procedure will be used to obtain information concerning the lipid environment in which neuronal uptake takes place. The effect of lipid modification on amphetamine uptake as well as on the cotransport of sodium with phenethylamines will be measured. Changes in transport will be correlated with change in membrane composition and fluidity changes. By studying in detail the mechanisms by which perturbations of nerve endings can change transport characteristics, the overall role of this important transport process in neuronal function and in the action of amphetamine-like drugs will be better understood.